Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The bcl-2 protooncogene encodes a 26-kD protein that extends cell survival by blocking apoptosis. This protein has been found to be overexpressed in neoplastic neural cell lines, although its expression in reactive and neoplastic astrocytes in vivo has not been well characterized. The authors hypothesized that bcl-2 oncoprotein expression in gliomas might be positively correlated with the tumor's degree of malignancy. Sixty-three gliomas of various subtypes and histological grades were immunostained by bcl-2 protein and the percentage of positive cells was quantitatively assessed. All tumors contained neoplastic cells that were immunoreactive for the bcl-2 protein (range of cell positivity 1%-53%). It was found that bcl-2 expression did not vary significantly as a function of tumor subtype or grade (p < 0.1, one-way analysis of variance (ANOVA) on ranks) as compared to the cell proliferation marker Ki-67 (MIB-1) in which a very significant correlation with tumor grade was noted (p < 0.0000001, one-way ANOVA on ranks). In fact, the highest percentage of bcl-2 immunoreactive cells was noted in low-grade gliomas, that is, in juvenile pilocytic astrocytomas and oligoastrocytomas. The specificity of bcl-2 overexpression was also assessed in 10 nonneoplastic lesions associated with prominent reactive astrocytosis. In nine of these cases (90%), bcl-2-positive reactive astrocytes were observed, often in large numbers, whereas relatively few Ki-67 immunoreactive cells were noted. The authors conclude that bcl-2 oncoprotein expression as assessed immunohistochemically does not correlate with glial tumor type or grade and its overexpression is not confined only to neoplastic conditions. Instead, the finding of robust bcl-2 expression in low-grade glial tumors and in reactive astrocytes warrants the inference that resistance to apoptosis is a nonspecific finding in astrocytes associated with both reactive and neoplastic conditions.
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PMID:Expression of bcl-2 in reactive and neoplastic astrocytes: lack of correlation with presence or degree of malignancy. 749 Jun 15

In an effort to optimize immunocytochemical methods to evaluate cell kinetics in brain tumors, we studied two newly-developed antibodies which react with formalin resistant epitopes of Proliferating Cellular Nuclear Antigen (PCNA) and Ki-67. These results were compared with standard flow cytometric cell cycle data from the same tumor specimens to determine if these methods correlate with each other, and whether retrospective analysis using these antibodies is feasible for cell kinetic analysis of brain tumors. Thirty-one specimens of glial tumors submitted for flow cytometry during 1992 were also reacted with antibodies to PCNA (PC-10) and Ki-67 (MIB-1). Flow cytometry scores for S-phase Fraction were compared with immunocytochemical scores for both antibodies, using an arbitrary rating of 1 (low, < 4%), 2 (intermediate, 4-6%), 3 (high, > 6%), and 1 (< 25% positive), 2 (26-75% positive), 3 (> 75% positive), respectively. MIB-1 results were found to correlate significantly with the S-phase fraction as determined by flow cytometry. The MIB-1 data showed a trend toward underestimating, i.e., lower scores, the proliferative index compared with flow cytometry. There was less of a correlation between PC-10 antibody scores and flow cytometry S-phase fraction, as PC-10 immunostaining typically overestimated the proliferative rate of brain tumors when compared with flow cytometry. There was an exact correlation between PC-10 and MIB-1 in only 4 cases, whereas in the remaining specimens, PC-10 results were always higher than MIB-1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Analysis of proliferative grade in glial neoplasms using antibodies to the Ki-67 defined antigen and PCNA in formalin fixed, deparaffinized tissues. 756 3

Large gemistocytic cells are well-known elements of glial tumors. Recently, miniature gemistocytic cells and neoplastic glial fibrillary acidic protein (GFAP)-positive oligodendroglial cells, which are regularly seen in oligodendrogliomas, have been termed "transitional cells". The proliferative activity of the gemistocytic cell types and the GFAP-positive (gliofibrillary) oligodendrocytes was determined in eight astrocytomas, seven gemistocytic astrocytomas, eight glioblastomas, two monstrocellular glioblastomas, seven oligodendrogliomas and three mixed oligo-astrocytomas by immunohistochemical staining of the proliferation marker MIB-1 in combination with immunostaining for GFAP. Both large gemistocytic cells and the transitional cells showed cytoplasmic GFAP-positive staining. Neither in the classic gemistocytes nor in the minigemistocytes nuclear immunostaining for the MIB-1 antibody was observed. In contrast, MIB-1 staining was seen in the gliofibrillary oligodendrocytes. It is concluded that both large and miniature gemistocytic cell types contrast with gliofibrillary oligodendrocytes by their inability to proliferate.
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PMID:Proliferation of gemistocytic cells and glial fibrillary acidic protein (GFAP)-positive oligodendroglial cells in gliomas: a MIB-1/GFAP double labeling study. 877 53

A total resection of a left frontal lobe tumor in a 26-year-old man revealed differentiated ganglioglioma with small foci of atypical glial cells exhibiting mild atypia. Six and one-half years later, a large, well-demarcated tumor recurred; at that time, histological analysis revealed both typical ganglioglioma and highly cellular anaplastic areas, the latter predominating. Although the patient subsequently underwent total and subtotal resections, radiation therapy, and chemotherapy, tumors continued to recur at progressively shorter intervals and he died at the age of 35 years. Biopsies of tissue obtained at the last three resections and the autopsy revealed only anaplastic tumor cells. Routine histological examinations indicated that these tumors were uniformly composed of undifferentiated cells. However, pathological studies using immunohistochemical analysis, electron microscopy, and immunoblot analysis demonstrated that a small number of recurrent anaplastic cells had astrocytic features. Results of Ki-67/MIB-1 labeling and silver nucleolar organizer region counts for those cells were high for glial tumors. A retrospective study of the initial tumor showed slightly high MIB-1 labeling for atypical glial cells. This case is characterized by pathological findings of recurrent tumors that correspond to an unusual form of malignant glioma exhibiting slight astrocytic differentiation. The present case suggests that a longer follow-up period ( > 5 years) is necessary in cases of ganglioglioma with mild atypia and that careful examinations, including proliferating potential analysis of initial tumor cells, could be important for the diagnosis and treatment of ganglioglioma.
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PMID:Recurrent anaplastic ganglioglioma: pathological characterization of tumor cells. Case report. 884 72

Well-differentiated astrocytomas may transform into malignant astrocytomas in time. In surgical specimens, when the histological picture strictly corresponds to that of grade II glioma, the transformation is unpredictable. Clinically, the bad outcome of a quota of astrocytomas is a well known phenomenon. The use of proliferation markers, and recently of MIB-1 LI, for detecting the proliferation potential comes out to be a useful tool for prognosis. A survival analysis of fifty astrocytomas grade II according to the WHO classification was performed with univariate and multivariate analysis of a series of clinical and histological parameters. MIB-1 LI was calculated and compared with all the other parameters. A cut-off of 8% of MIB-1 LI divided the astrocytomas in two groups with significantly different survival (p = 0.0066): median survival time of 1062 versus 1686 days. According to multivariate analysis MIB-1 LI resulted to be an independent factor (p = 0.002) along with extension of surgical removal (partial versus total), postoperative Karnofsky status (> or = 70 versus < 70) and age (< or = 30 versus > 30). The interpretation of well-differentiated astrocytomas with high MIB-1 LI is that the increasing number of cycling cells precedes phenotypic transformation. MIB-1 LI can be used as a prognostic factor.
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PMID:Proliferative activity and prognosis of low-grade astrocytomas. 921 51

The grading of glial tumors has traditionally relied on histological assessment, but the distinction between grade II and grade III gliomas is still a subject of debate. We examined the value of the monoclonal antibody MIB-1 (Ki-67) labeling index (LI) in the differentiation between grade II and grade III gliomas by either the 1993 WHO grading scheme or the St. Anne-Mayo grading scale. The MIB-1 Li in the most densely labeled areas from 80 diffuse cerebral hemispheric gliomas was determined. The tumors included 16 grade II, 31 grade III and 33 grade IV gliomas by the WHO scale. The mean LIs (%) were 0.88 +/- 0.29 for grade II, 8.75 +/- 1.71 for grade III, and 9.12 +/- 1.55 for grade IV gliomas. Analysis of variance indicated a significant difference in mean LIs between grades II and III and grades II and IV (p < or = 0.0001), but not between grades III and IV. Seven tumors were classified differently by the 2 systems (grade III by WHO, but grade 2 by St. Anne-Mayo), and all had MIB-1 LI over 3%. Univariate analysis showed that MIB-1 LI with a cut-off point at 1.5% was a significant prognostic factor (p < or = 0.0005). High tumor grade (WHO, p < or = 0.0002; St. Anne-Mayo, p < or = 0.0006) and patient age > 50 (p < or = 0.0001) were also significant factors for shorter survival. Using Cox Regression Multivariate Analysis, MIB-1 LI > 1.5% was a significant independent predictor of shorter disease survival when paired with tumor grade (p < or = 0.032), patient age (p < or = 0.0065), or gender (p < or = 0.0007). We conclude that the MIB-1 immunoreactivity is useful in distinguishing grade II from grade III gliomas, and maybe more sensitive in assigning aggressive gliomas to grade III than the St. Anne-Mayo grading system.
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PMID:Use of MIB-1 (Ki-67) immunoreactivity in differentiating grade II and grade III gliomas. 925 55

Proliferative activity in 78 glioma specimens was assessed immunohistochemically by determining proliferating index of tumor cells (PTC-PI) and endothelial cells (PEC-PI) using the MIB-1 monoclonal antibody. The PTC-PI of anaplastic astrocytoma (9.0 +/- 5.8: mean + standard deviation) was significantly higher than that of astrocytoma (1.2 +/- 0.4, < 0.01), and lower than that of glioblastoma multiforme (12.0 +/- 5.6, < 0.05). We then compared PTC-PI values with the prognosis of patients with malignant glioma (both glioblastoma and anaplastic astrocytoma). Kaplan-Meier survival rate analysis demonstrated higher survival rates in patients with less than 8.0% of PTC-PI at 5 and 10 years (p < 0.05). These results suggested PTC-PI provides useful information which may allow better assessment of the biological behaviour and clinical prognosis of glioma, in addition to histological grading. While the average PEC-PI value (3.3) was lower than that of PTC-PI (7.0), there was a significantly close relationship between them (p < 0.01), fostering the developments novel therapies directed towards suppression of microvascular regeneration.
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PMID:Proliferative potentials of glioma cells and vascular components determined with monoclonal antibody MIB-1. 926 40

Cyclin D1 (cycD1) expression was defined immunohistochemically using monoclonal antibody DCS-6 and polyclonal antiserum H-295 in 50 glioma biopsies. The number of positive nuclei was higher for H-295 than for DCS-6, with a ratio of 3:1. The labelling index (LI) was compared to the grade of histological malignancy and to Ki-67 MIB-1 LI. The LI for cycD1 increased with histological malignancy, in parallel with the increase in MIB-1 LI. In most tumours, the maximum LI for cycD1 and MIB-1 were found in the same areas. The mean MIB-1 LI: mean cycD1 LI ratio does not vary in the three grades of astrocytic tumours. However, in this study the correlation between the two LIs was not statistically significant. Staining for cycD1 antigen does not necessarily imply that the gene is overexpressed since other molecular mechanisms can also be responsible for cell cycle deregulation. In invasive areas, the cycD1 LI is frequently higher than in solid tumour, either because more tumour cells are positive or because reactive astrocytes and activated microglia express cycD1. The relative contribution of neoplastic and reactive cells remains to be defined.
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PMID:Cyclin D1 expression in gliomas. 949 46

Proliferative activity in 78 glioma specimens was assessed immunohistochemically by determining proliferating index of tumor cells (PTC-PI) and endothelial cells (PEC-PI) using the MIB-1 monoclonal antibody. The PTC-PI of anaplastic astrocytoma (9.0 +/- 5.8: mean +/- standard deviation) was significantly higher than that of astrocytoma (1.2 +/- 0.4, < 0.01), and lower than that of glioblastoma multiforme (12.0 +/- 5.6, < 0.05). We then compared PTC-PI values, patients' age and extent of tumor resection with the prognosis of patients with malignant glioma (both glioblastoma and anaplastic astrocytoma). Kaplan-Meier survival rate analysis demonstrated higher survival rates in patients with less than 8.0% of PTC-PI at 5 and 10 years (p < 0.05). The mean age of patients who survived more than a year was lower than that of patients who died within a year (53.0 y.o., vs. 59.7 y.o., p < 0.01). Total or subtotal resection of the tumor was more often performed in the former than latter patients (51% vs. 21%, p < 0.01). These results suggested PTC-PI provides useful information which may allow better assessment of the biological behavior and clinical prognosis of glioma, in addition to histological grading, patients' age and extent of tumor resection. While the average PEC-PI value (3.3) was lower than that of PTC-PI (7.0), there was a significantly close relationship between PTC- and PEC values (p < 0.01), providing an impetus to develop novel therapies directed toward suppression of microvascular regeneration.
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PMID:Proliferative potentials of glioma cells and vascular components determined with monoclonal antibody MIB-1. 950 11

Immunohistochemistry (IHC) has provided major insights about the classification of brain tumors by identifying cellular markers of phenotype and about tumor growth potential with nuclear markers of proliferation. In situ hybridization (ISH) research shows promise for diagnostic applications in tumor classification. The avidin-biotin conjugate IHC procedure is highlighted for diagnostic use on routinely processed clinical specimens. The immunophenotypes of brain tumors are tabulated in reference to their common IHC markers. Tumors that have been correctly classified by their IHC phenotypes include the giant-cell glioblastoma, primary brain lymphoma, and central neurocytoma. Phenotypes that may be more definitively detected by ISH, such as pituitary hormone, immunoglobulin light chain, and collagen messages are described. IHC of nuclear proliferation markers correlates with grade of malignancy, predicts tumor growth potential, and is prognostic for patient survival. The incorporation of bromodeoxyuridine, the expression of proliferating cell nuclear antigen, and the expression of Ki-67 antigen detected by MIB-1 antibody are compared in regard to their cell cycle activity and labeling index determinations. Fluorescence in situ hybridization (FISH) of brain tumor interphase nuclei and chromosomes is described. Abnormal FISH signals of specific chromosomes are associated with different types of brain tumors, with different grades of malignancy, and with mesenchymal drift of glioma cells in culture.
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PMID:Insights about brain tumors gained through immunohistochemistry and in situ hybridization of nuclear and phenotypic markers. 960 6


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